Inflammation in Atherosclerotic Cardiovascular Disease: A Heart on Fire

Abstract

Interest in the role of inflammation in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD) has continued to grow over the past several decades. As the population continues to age, and the burden of ASCVD continues to climb, researchers and clinicians continue to look for novel treatments and targets to reduces the burden and mitigate the effects of ASCVD. In this thesis, the role of inflammation in the pathogenesis of ASCVD was further assessed along with an assessment of potential therapies that could be used to mitigate the effects of inflammation on the cardiovascular system. This thesis comprises six main sections: (1) a systematic review and network meta-analysis looking at the relative efficacy of anti-inflammatory therapies for the treatment of cardiovascular disease; (2) an observational cross-sectional study to evaluate inflammatory biomarkers in patients with acute cardiovascular events and remote cardiovascular events; (3) a protocol for a double-blind randomized controlled trial to evaluate the efficacy of the anti-inflammatory agent, colchicine, in reducing vascular inflammation; (4) a cost-effectiveness analysis of the use of colchicine for ASCVD; (5) a cohort study evaluating the effect of biologic therapy on vascular inflammation in patients with psoriatic-arthritis/dermatologic; and (6) a cohort study looking at the effect of low-dose statin therapy on vascular inflammation in patients with human-immunodeficiency virus (HIV). While inflammation has long been recognized to be an etiological player in the pathogenesis of ASCVD, until recently, studies exploring inflammation as a potential treatment target have been lacking. This has changed in recent years, with an explosion of studies evaluating anti-inflammatory therapies for the treatment of CV disease. The relative efficacy of these therapies remains unknown. Additionally, it remains unknown whether therapies targeting the inflammatory pathway should be used in all patients with ASCVD (or at high-risk of ASCVD) or if we should specifically target high-risk subgroups. Lastly, information with respect to the cost-efficacy of these therapies from a Canadian health-care system perspective remain needed.